深部浸润型与表浅型子宫内膜异位症者腹腔液Th1、Th2细胞因子变化

目的:研究深部浸润型与表浅型子宫内膜异位症(EMs)临床特征以及腹腔液Th1、Th2细胞因子的表达差异。方法:收集术后病理证实诊断为EMs患者的临床资料及其腹腔液,根据术中诊断分为:表浅型(腹膜型,n=30)、深部浸润型(n=16);以同期因输卵管因素不孕症行腹腔镜探查的妇女(n=16)为对照组。用ELISA法测定3组腹腔液中IL-2、IL-4、IL-6、IL-10、TNF-α、IFN-γ的表达差异性。结果:表浅型EMs患者年龄较轻、不孕率高、腹水发生率高,而性交痛则是深部浸润型EMs患者的典型临床特征。与对照组相比,EMs组腹腔液中IL-4、IL-6、IL-10、TNF-α表达均升高,IFN-γ在EMs组表达均降低。IL-2仅在深部浸润型EMs组升高;深部浸润型EMs组与表浅型EMs组之间对比,IL-6在表浅型EMs的升高明显(P<0.01),IL-10与TNF-α则在深部浸润型EMs组升高明显(P<0.01),IFN-γ在深部浸润型EMs组下降更为明显(P<0.01),IL-4在2个EMs组间表达无差异。结论:在表浅型与深部浸润型EMs的发病机制中,两者具有不同的免疫学改变。     

Serum and peritoneal fluid levels of interleukin-6 and interleukin-37 as biomarkers for endometriosis

This study aimed to compare the levels of interleukin (IL)-1β, IL-6, IL-10, and IL-37 in the serum and peritoneal fluid of women with and without endometriosis. In addition, it aimed to determine the diagnostic values of the cytokines with significantly different concentrations. The levels of IL-1β, IL-6, IL-10, and IL-37 in the serum and peritoneal fluid samples of 40 women with endometriosis and 32 women without endometriosis were measured using an enzyme-linked immunosorbent assay. The serum and peritoneal fluid levels of IL-1β and IL-10 were not statistically significantly different between the endometriosis and control groups. The IL-6 and IL-37 levels in the serum and peritoneal fluid were higher in the endometriosis group than in the control group, and they were correlated with the stage of endometriosis. The AUC for the IL-37 was 0.897 for the serum and 0.934 for the peritoneal fluid, while the AUC for the IL-6 was 0.905 for the serum and 0.952 for the peritoneal fluid. Our results suggest that the serum and peritoneal fluid IL-6 and IL-37 levels were significantly increased in the endometriosis patients, indicating that these cytokines may serve as biomarkers for the diagnosis of endometriosis.     

Th1/Th2细胞因子在不同临床特征的EMs患者差异性表达

目的:研究Th1、Th2各细胞因子在不同临床特征的子宫内膜异位症(EMs)患者差异性表达。方法:收集120例拟诊为"EMs"的患者临床资料。患者均于卵泡期行腹腔镜手术探查,术后经病理证实EMs者87例,非EMs者33例,将EMs组和非EMs组患者分别以主要主诉及临床特征如不孕、痛经/慢性盆腔痛、月经异常、卵巢受累进行再分组,应用ELISA法检测患者腹腔液中IL-2、IL-4、IL-6、IL-10、TNF-α、IFN-γ的表达。结果:以"痛经/盆腔痛"为主要临床特征的EMs组与非EMs组患者腹腔液TNF-α表达有显著差异,显示其与EMs盆腔痛有相关性(P=0.00);以"不孕"为主要临床特征的EMs组与非EMs组患者腹腔液IL-2表达有统计学差异(P=0.03);在检查有盆腔包块或月经异常的患者,术中探查卵巢子宫内膜异位囊肿或明确卵巢受累者的腹腔液IL-10在EMs组与非EMs组表达有统计学差异(P=0.01)。结论:在EMs患者Th1/Th2漂移的免疫异常中,不同的细胞因子在发病和临床特征的形成中发挥作用。     

The evaluation of IL-12 levels in peritoneal fluid and serum of women with endometriosis

We studied levels of IL-12 in peritoneal fluid and serum in patients with minimal, advanced and recurrent endometriosis compared to women without endometriotic lesions in pelvis minor. The aim of the study was to determine whether level of IL-12 detected in peritoneal fluid or serum changes with grading of severity of endometriosis. To assess IL-12 levels immunosorbent ELISA was used. There were no statistically significant differences in IL-12 levels in peritoneal fluid nor in serum in any of studied groups. There was higher concentration (without statistical significance) of IL-12 in peritoneal fluid of healthy women compared to women with endometriosis.     

Vascular endothelial growth factor and interleukin-6 in peritoneal fluid of women with endometriosis

OBJECTIVE(S): To determine [1] vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) levels in peritoneal fluid from women with endometriosis and compare them with those from oral contraceptive (OC) users and normal cycling women and [2] any correlation between VEGF and IL-6 concentrations. DESIGN: Controlled clinical study. SETTING: University medical center. PATIENT(S): Patients undergoing laparoscopy for infertility or other benign gynecologic conditions. INTERVENTION(S): Peritoneal fluid samples were collected. MAIN OUTCOME MEASURE(S): Levels of VEGF and IL-6 in peritoneal fluid were determined. RESULT(S): Compared with normal controls or women with less severe endometriosis (implant scores of 5 or less), women with more advanced endometriosis (implant scores of 6 or more) have elevated VEGF and IL-6 levels in peritoneal fluid. Compared with normal controls, markedly suppressed IL-6 but similar VEGF levels were found in peritoneal fluid from OC users. Neither VEGF nor IL-6 varied cyclically in normal women or those with endometriosis. There was no correlation between levels of VEGF and IL-6 in peritoneal fluid. There was no correlation between implant scores and VEGF or IL-6 levels. CONCLUSION: The inflammation associated with endometriosis, through increased levels of peritoneal fluid VEGF, may promote angiogenesis for the progressive growth of endometriosis. Effective treatment of endometriosis by combination estrogen-progestin pills may involve the suppression of such inflammatory responses.     

Association of interleukin-6 and estradiol with hepatocyte growth factor in peritoneal fluid of women with endometriosis

BACKGROUND: Different cytokines and ovarian steroid hormones have been reported to regulate the growth and maintenance of endometriosis. We determined the relationship between peritoneal fluid concentrations of interleukin-6, ovarian steroids and hepatocyte growth factor in different revised American Fertility Society (AFS) staging and morphologic appearances of endometriosis. METHODS: Peritoneal fluid was collected from 30 women with endometriosis and 20 women without endometriosis during laparoscopy, and hepatocyte growth factor, interleukin(IL)-6 and ovarian steroids were measured in peritoneal fluid. The concentrations of hepatocyte growth factor and IL-6 in peritoneal fluid were measured by ELISA, and that of estradiol and progesterone by using the immulyze-enzyme amplified luminescence system. Changes in peritoneal fluid concentrations of hepatocyte growth factor, IL-6, estradiol and progesterone in different stages and morphologic appearances of endometriosis were examined to demonstrate their differences in early and advanced endometriosis. RESULTS: Peritoneal fluid levels of hepatocyte growth factor in women with stage I-II endometriosis were significantly higher than in both women with stage III-IV endometriosis and without endometriosis. A similar significant increase in stage I-II endometriosis was also observed for IL-6 and estradiol. When we divided the women according to different morphologic appearances of endometriosis, we found significantly higher concentrations of hepatocyte growth factor (HGF), IL-6, estradiol and progesterone in women containing red lesions compared with other pigments or without endometriosis. A positive correlation was observed between peritoneal fluid levels of IL-6 and hepatocyte growth factor only but not between other markers. Although estradiol levels in peritoneal fluid showed an increased tendency to elevate in the proliferative phase of endometriosis women, hepatocyte growth factor and progesterone displayed higher concentrations in the secretory phase of the menstrual cycle. After adjusting different variables in peritoneal fluid, multiple analysis of covariance indicated that hepatocyte growth factor levels in peritoneal fluid were independently involved in the red morphologic activity of endometriosis. CONCLUSIONS: Early staging and red color appearance of endometriosis are associated with the elevation in peritoneal fluid concentrations of hepatocyte growth factor, IL-6 and estradiol, demonstrating the combined effect of these cytokines and ovarian steroids in the production of hepatocyte growth factor from endometrial tissues in active endometriosis.     

Cytokine profiles in serum and peritoneal fluid from infertile women with and without endometriosis

OBJECTIVE: To study the serum and peritoneal fluid cytokine profiles in infertile women with minimal/mild active endometriosis. METHODS: Fifty-seven consecutive infertile women undergoing laparoscopy for unexplained infertility had peritoneal fluid and serum samples obtained at the time of laparoscopy. The levels of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 beta (IL-1 beta), vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotatic protein-1 (MCP-1), RANTES, platelet derived growth factor (PDGF), soluble Fas (sFas), and soluble Fas Ligand (sFasL) in peritoneal fluid and serum were measured to compare the concentration in both biological fluids, in women who have minimal/mild red endometriosis using women with no endometriosis as controls. RESULTS: Peritoneal fluid levels of MCP-1, IL-8 and IL-6 were significantly higher in the endometriosis group (P < 0.012, P = 0.003, and P = 0.015, respectively). There was no significant difference in the peritoneal fluid levels of IL-1 beta, TNF-alpha, RANTES, VEGF, PDGF, sFas and sFasL in the two groups. Although serum levels of IL-8 were higher in women with endometriosis, the difference was not significant (P = 0.07). Serum levels of PDGF, IL-6, RANTES, IL-1 beta, TNF-alpha, and sFas, were not significantly different in the two groups. CONCLUSION: The elevated levels of MCP-1, IL-6, and IL-8 in peritoneal fluid but not serum may indicate the importance of local macrophage activating factors in the pathogenesis of endometriosis.     

Different concentrations of interleukins in the peritoneal fluid of women with endometriosis: relationships with lymphocyte subsets.

The present study explored the possible relationships between immune cell subsets and interleukin (IL)-12 or IL-13 levels in the peritoneal fluid of patients with and without endometriosis. Peritoneal fluid samples were obtained from 80 women while they were undergoing laparoscopy for pain, infertility, tubal ligation or re-anastomosis. The American Fertility Society scoring system was used to determine the extension of endometriosis. The peritoneal fluid mononuclear cells were analyzed for immunophenotyping using cytometry, whereas peritoneal fluid concentrations of interleukins were measured using two ultrasensitive commercially available enzyme-linked imnunosorbent assay kits. Significantly higher peritoneal fluid IL-12 levels were found in women with moderate or severe endometriosis (stages III and IV) than in healthy controls (p < 0.01). Conversely, subjects with endometriosis showed remarkably lower peritoneal fluid IL-13 concentrations than controls, independent of the severity of the disease (p < 0.05). Considering immune system effectors, patients with endometriosis presented a significantly higher peritoneal fluid CD8+/CD4+ ratio when compared with healthy controls. Moreover, the number of peritoneal fluid CD8+ and CD4+ activated T cells was significantly lower in the former than in the latter group, independent of the endometriosis stage. Connections were observed between peritoneal fluid interleukins and peritoneal fluid T cells: both patients with endometriosis and controls presented an inverse correlation between peritoneal fluid activated T cells and IL-13 levels, and a direct correlation between peritoneal fluid T cells and IL-12 concentrations. These data seem to suggest that a reciprocal modulation exists between peritoneal fluid cytokines and T lymphocyte subsets in patients with endometriosis.     

Increased levels of human neutrophil peptides 1, 2, and 3 in peritoneal fluid of patients with endometriosis: association with neutrophils, T cells and IL-8

Endometriosis is a common gynaecological disorder characterized by the presence of endometrial tissue outside the uterine cavity. This disease is associated with pelvic inflammation and displays some features of autoimmune disorder. Human neutrophil peptides 1, 2, and 3 (HNP 1-3) belonging to α-defensin family play a crucial role in innate immunity against infections and may exert immunoregulatory effects. They may play a role in various inflammatory reactions; however, their role in endometriosis has not been studied. Therefore, the aim of the present study was to evaluate HNP 1-3 in the peritoneal fluid of 67 patients with endometriosis and 16 healthy control women in relation to peritoneal leukocyte subpopulations (neutrophils, T cells, and macrophages) and inflammatory cytokines (IL-6 and IL-8). HNP 1-3, IL-6 and IL-8 were evaluated in the peritoneal fluid by specific enzyme-linked immunosorbent assays (ELISA), and peritoneal leukocyte subpopulations were evaluated by flow cytometry. We found that the levels of HNP 1-3 were significantly increased in the peritoneal fluid of endometriosis patients, compared with control women, and correlated with severity of the disease. Endometriosis was also associated with increased concentrations of peritoneal neutrophils. In endometriosis the levels of HNP 1-3 strongly correlated with concentrations of neutrophils, T cells and IL-8. HNP 1-3 levels were not associated with peritoneal IL-6 or macrophages. These data suggest that HNP 1-3 and neutrophils might play a role in immunopathogenesis of endometriosis and may be worth evaluating as targets for anti-endometriosis therapy.     

Altered expression of interleukin-18 in the peritoneal fluid of women with endometriosis

OBJECTIVE: Peritoneal fluid (PF) inflammatory factors may participate in the pathogenesis of endometriosis. The aim of this study was to investigate PF interleukin (IL)-18 levels in women with and without endometriosis. DESIGN: Controlled clinical study. SETTING: Women undergoing laparoscopy at a university hospital. PATIENT(S): Fifty women with previously untreated endometriosis, 8 women on GnRH agonists for endometriosis, and 18 control women with normal pelvic anatomy who were undergoing tubal ligation. INTERVENTION(S): Peritoneal fluid IL-18 levels as measured by ELISA. MAIN OUTCOME MEASURE(S): Peritoneal fluid IL-18 levels. RESULT(S): Peritoneal fluid IL-18 levels were significantly higher in women with previously untreated endometriosis (mean +/- SEM, 91.1 +/- 6.5 pg/mL) than in control women (59.4 +/- 2.0 pg/mL). Interestingly, women with superficial (100.0 +/- 10.2 pg/mL) and deep peritoneal implants (94.0 +/- 10.8 pg/mL) had significantly higher PF IL-18 levels than did women with endometriomas (57.8 +/- 1.8 pg/mL). Similarly, women with stage I-II endometriosis (97.3 +/- 8.0 pg/mL), but not women with stage III-IV endometriosis (74.9 +/- 9.9 pg/mL), had significantly higher PF IL-18 levels than did control women. Peritoneal fluid IL-18 levels were significantly higher in the luteal phase than in the follicular phase but did not discriminate between women with pelvic pain or infertility. CONCLUSION(S): Peritoneal fluid IL-18 is elevated in women with peritoneal, minimal- to mild-stage endometriosis.     

VEGF, TNF-alpha and IL-6 in the peritoneal fluid of women with unexplained infertility

Unexplained infertility is an important problem in diagnosis and therapy in everyday gynecologist's practice. Looking for possible reasons of the unexplained infertility we studied the concentrations of selected cytokines (VEGF, TNF-alpha and IL-6) in the peritoneal fluid of women suffering from the unexplained infertility. We compared the results in the studied group with the control group and with the patients with endometriosis. Immunological disorders of the peritoneal fluid in endometriosis are thought to take part in its pathomechanism. Our results suggest that the levels of one of the main factors of endothelium proliferation (VEGF) in the peritoneal fluid from women with unexplained infertility and women with endometriosis are comparable. Concentration IL-6 and TNF-alpha in the peritoneal fluid in case of unexplained infertility and control group was lower than in the endometriosis patients.     

Mouse embryo toxicity of IL-6 in peritoneal fluids from women with or without endometriosis

BACKGROUND: To determine whether there is a factor (or factors) in the peritoneal fluid of endometriosis patients that impairs embryo growth and embryo implantation. METHODS: Growth and development of two-cell mouse embryos which were cultured in media with peritoneal fluid from women with or without endometriosis and interleukin-1-beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels in conditioned media were measured. RESULTS: The blastocyst rate in the non-endometriosis group was 46.4 +/- 31.1%, and that of the endometriosis group was 54.6 +/- 28.7%. Logistic regression analysis using the criteria of blastocyst development in 454 embryos, showed that the peritoneal fluid from endometriosis could promote (p=0.015) but IL-6 could arrest embryo growth to blastocyst (p=0.025). IL-1beta and TNF-alpha levels had no significant effect on blastocyst formation. CONCLUSION: Peritoneal fluid from women with endometriosis was not toxic to mouse embryo development. However, IL-6 in the peritoneal fluid deteriorated the growth and development of mouse embryos.     

Decreased peritoneal concentrations of interleukin-15 in women with advanced stage endometriosis

OBJECTIVE: To assess the concentrations of interleukin-15 (IL-15) in peritoneal fluid from women with endometriosis and fertile disease-free controls. STUDY DESIGN: Peritoneal fluid samples were obtained from 50 women with endometriosis and 29 fertile women having tubal ligation. Concentrations of IL-15 were measured. RESULTS: The mean (S.D.s) concentration of IL-15 in peritoneal fluid was 11.17 pg/mL (3.89) for women with endometriosis, and 12.59 pg/mL (4.11) for fertile disease-free controls. The difference of peritoneal IL-15 concentrations between endometriosis and control women was not statistically significant. However, peritoneal IL-15 concentrations were significantly lower in women with moderate/severe endometriosis when compared with those in women with minimal/mild endometriosis, and in controls (P<0.05). In addition, peritoneal IL-15 concentrations did not correlate with the phase of menstrual cycle in endometriosis or control women. CONCLUSIONS: Our results suggest that the decreased peritoneal IL-15 concentrations in women with moderate/severe endometriosis imply a role of IL-15 in the pathogenesis of advanced endometriosis as compared to those with minimal/mild endometriosis and fertile disease-free controls.     

Lymphocyte activity in the presence of peritoneal fluid from fertile women and infertile women with and without endometriosis

Peritoneal fluid from women with endometriosis, unexplained infertility, and fertile controls were compared to one another and to normal human serum for effects on lymphocyte proliferation in vitro. Peritoneal fluid samples were also assayed for both interleukin-1 and interleukin-2. All peritoneal fluid samples significantly enhanced lymphocyte proliferation in both mitogen-stimulated and unstimulated cultures compared with serum controls. Mitogen-induced leukocyte proliferation was higher in the presence of peritoneal fluid from women with endometriosis compared with other samples. Five out of 23 samples from endometriosis patients contained elevated levels of interleukin-1 and three out of 23 contained elevated levels of interleukin-2. Six out of eight peritoneal fluid samples from unexplained infertility patients also had elevated levels of interleukin-2; samples from fertile women did not contain elevated levels of either cytokine. Our data indicate that peritoneal fluid from women with endometriosis and unexplained infertility support the activation and proliferation of lymphocytes. Leukocyte products may locally affect the progression of disease and fertility.     

Cytokine profiles in autologous peritoneal fluid and peripheral blood of women with deep and superficial endometriosis

In a preliminary study the hypothesis was tested that cytokine profiles in peripheral blood were higher in women with deep infiltrating endometriosis and cytokine profiles in peritoneal fluid were higher in women with superficial endometriosis. Thirteen women of reproductive age having laparoscopy for infertility (n=9), pain (n=3) or combined pain and infertility (n=1). Peripheral blood and peritoneal fluid were obtained and analyzed for Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), Interleukin-10 (IL-10), Transforming Growth Factor-betal (TGFβ1), and Interferon-gamma (IFN-γ). No significant cytokine differences were observed in either peritoneal fluid or peripheral blood between IL-6, TGFβ1, IFNγ, TNF-alpha and IL-10 of women with superficial endometriosis (n=7) and women with deeply infiltrating endometriosis (n=6). The results of this preliminary study do not show significant differences in peripheral blood and peritoneal fluid cytokine levels between women with deep infiltrating endometriosis compared to women with superficial disease. Future studies with increased sample size are required to either confirm or refute these preliminary findings. Received: 5 January 2000 / Accepted: 14 August 2000     

Concentrations of interleukin (IL)-1alpha, IL-1 soluble receptor type II (IL-1 sRII) and IL-1 receptor antagonist (IL-1 Ra) in the peritoneal fluid and serum of infertile women with endometriosis

OBJECTIVE: Endometriosis is an immune system-related gynaecological disease, characterised by an increase in number and activation of peritoneal macrophages. One of macrophage-derived factors is interleukin (IL)-1. The effects of IL-1 are inhibited by IL-1 receptor type II (IL-1 RII), soluble forms of IL-1 RII (IL-1 sRII) and IL-1 receptor antagonist (IL-1 Ra). The aim of our work was to study the IL-1alpha, IL-1 sRII and IL-1 Ra levels in the peritoneal fluid (PF) and serum of women with endometriosis in relation to stage of disease. STUDY DESIGN: Concentrations of IL-1alpha, IL-1 sRII and IL-1 Ra were measured by ELISA assay in the PF and serum of 58 women; 43 with and 15 without endometriosis (control group). RESULTS: Elevated PF and serum IL-1alpha and IL-1 Ra levels in the women with endometriosis in comparison with the control group were observed. IL-1 sRII levels in PF and serum were higher in the controls than in the women with endometriosis. Concentrations of IL-1alpha and IL-1 sRII were higher in advanced endometriosis, but higher IL-1 Ra was observed in the early stage of the disease. CONCLUSION: Impairment of regulation IL-1 activity in the peritoneal fluid and serum of women with endometriosis may play an important role in the pathogenesis and development of the disease.     

子宫内膜异位症患者辅助性T细胞亚群免疫状态的研究

目的　探讨辅助性T细胞 (Th)亚群在子宫内膜异位症 (内异症 )发病中的作用。方法　采用酶联免疫吸附法检测 30例内异症患者 (内异症组 )及 2 0例非内异症患者 (对照 1组 )血清及腹腔液中白细胞介素 (IL) 2、6的水平 ;用免疫组化技术分别检测IL 2、IL 6在内异症组患者异位内膜组织和 10例子宫肌瘤患者 (对照 2组 )的正常子宫内膜组织中的表达。结果　内异症组患者血清及腹腔液中位数IL 6水平分别为 5 3、2 1ng/L ,对照 1组患者血清及腹腔液中位数IL 6水平分别为 2 5、0 9ng/L ,两组妇女血清和腹腔液中IL 6水平分别比较 ,差异均有统计学意义 (P <0 0 5 ) ;内异症组Ⅲ～Ⅳ期患者血清及腹腔液中位数IL 6水平分别为 13 6、4 1ng/L ,Ⅰ～Ⅱ期患者血清及腹腔液中位数IL 6水平分别为 3 7、1 6ng/L ,Ⅲ～Ⅳ期患者与Ⅰ～Ⅱ期患者血清及腹腔液中位数IL 6水平比较 ,差异均有统计学意义 (P <0 0 5 ) ;内异症组IL 2 /IL 6比值在血清及腹腔液中分别为 0 7、1 1,均分别低于对照组的 0 8、6 2 ,差异也有统计学意义 (P <0 0 5 )。内异症组患者腹腔液与血清IL 6水平呈正相关 (r =0 74 5 ,P <0 0 1) ,血清及腹腔液中IL 6水平与IL 2 /IL 6比值均呈负相关 (r =- 0 4 0 6 ,P <0 0 5 ;r =- 0 4 80 ,P <0 0 5 )     

Peritoneal fluid concentrations of interleukin-4 in relation to the presence of endometriosis, its stage and the phase of the menstrual cycle

BACKGROUND: Interleukin-4 (IL-4) is a cytokine with both stimulatory and inhibitory effects on the inflammatory system such as macrophage inhibition and T-cell activation. It is known to regulate several monocyte functions, including inhibition of the synthesis of cytokines such as IL-1, IL-6 and TNF-alpha as well as potentiating IL-8. METHOD: In an attempt to clarify the association between IL-4 and endometriosis, we measured the concentration of IL-4 in the peritoneal fluid of 52 women; 24 with endometriosis and 28 with no endometriosis, controlling for the phase of the cycle and the stage of disease. RESULTS: There was no difference in the concentrations of IL-4 between women with (n=28) and without endometriosis (n=24). No difference was found between the IL-4 concentrations in women with different stages of endometriosis. Levels of IL-4 did not show a difference according to the phase of the cycle in either group. CONCLUSION: Our results indicate no association between peritoneal fluid levels of IL-4 and endometriosis and hence suggest that IL-4 is not involved in the pathogenesis of endometriosis.     

Correlation of angiogenic cytokines-leptin and IL-8 in stage,type and presentation of endometriosis

Pelvic endometriosis is a chronic inflammatory disease with an immunological background. Yet there is paucity of contemporary research exploring both the angiogenic cytokines, leptin and IL-8 for a possible role in its pathophysiology. Objective: To compare levels of both leptin and IL-8 in peritoneal fluid (PF) in women with endometriosis vs. fertile controls and correlate with disease stage, type and symptoms. Materials and methods: PF from 58 women with endometriosis and 28 women undergoing tubal ligation was collected at laparoscopy and leptin and IL-8 levels were measured using ELISA. Results showed significantly higher levels of both cytokines in women with endometriosis. Significantly higher leptin and IL-8 levels were demonstrated in patients with early peritoneal (ASRM stage I and II) and advancing disease (ASRM stage III and IV), respectively. Levels of leptin/IL-8 were significantly lower in patients with endometrioma (4.8?ng/mL/32 pg/mL) vs. implants (13.0?ng/mL/68 pg/mL). There was no correlation of infertility or chronic pelvic pain with these levels. Conclusion: Both leptin and IL-8 levels are raised in PF of women with endometriosis reflecting inflammation and dysregulated immunomodulation. Higher levels of leptin were seen in early stages; IL-8 seems to stimulate the disease in a dose-dependent manner.     

Role of cytokines in endometriosis-associated infertility

Endometriosis, which is common in women of reproductive age, may affect fertility. It is also clear that mechanical disruption of the pelvic anatomy may cause infertility. However, our understanding of the association between the early stage of endometriosis and infertility remains incomplete. Bloody peritoneal fluid (PF) is frequently observed in the cul-de-sac of endometriosis patients and contains various biologically active factors. We found that the concentrations of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in PF from patients with endometriosis were significantly higher than that of patients with endometriosis. There were significantly positive correlations between the levels of TNF-alpha and IL-6. We compared the levels of these cytokines with regard to the R-AFS stages and scores, but no differences were observed. In contrast, these cytokines correlate with the number and extent of red color peritoneal endometriosis. TNF-alpha increased the expression of IL-6 messenger RNA and protein in endometriotic stromal cells derived from chocolate cyst in a dose-dependent manner. The addition of IL-6 inhibited the development of mouse preimplantation embryo and impaired sperm function. We concluded that increased levels of IL-6 in peritoneal fluid of patients with active red endometriosis might be related to endometriosis-associated fertility.